Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450

J. Capdevila; Y. R. Kim; C. Martin-Wixtrom; J R Falck; S. Manna; R. W. Estabrook

doi:10.1016/0003-9861(85)90768-4

Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450

J. Capdevila, Y. R. Kim, C. Martin-Wixtrom, J R Falck, S. Manna, R. W. Estabrook

Biochemistry

Research output: Contribution to journal › Article › peer-review

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Abstract

The regiospecificity of arachidonic acid oxygenation, catalyzed by rat liver microsomal fractions in the presence of NADPH, can be altered by animal pretreatment with a fibric acid type of hypolipidemic drug, ciprofibrate. While microsomal fractions isolated from either control or phenobarbital-treated animals oxygenate arachidonic acid to mainly epoxyeicosatrienoic acids (EETs), animal pretreatment with ciprofibrate results in an eightfold stimulation of ω and ω-1 oxidation, concomitant with a net decrease in the formation of both HETEs and EETs. The isomeric composition of the EETs and of the ω and ω-1 oxidation products formed is also dependent on the type of animal pretreatment. Associated decreases in the amounts of HETEs and the rate of hydrogen peroxide formation suggests a modification of the "uncoupler action" of arachidonic acid during the function of different cytochromes P-450.

Original language	English (US)
Pages (from-to)	8-19
Number of pages	12
Journal	Archives of Biochemistry and Biophysics
Volume	243
Issue number	1
DOIs	https://doi.org/10.1016/0003-9861(85)90768-4
State	Published - Nov 15 1985

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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title = "Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450",

abstract = "The regiospecificity of arachidonic acid oxygenation, catalyzed by rat liver microsomal fractions in the presence of NADPH, can be altered by animal pretreatment with a fibric acid type of hypolipidemic drug, ciprofibrate. While microsomal fractions isolated from either control or phenobarbital-treated animals oxygenate arachidonic acid to mainly epoxyeicosatrienoic acids (EETs), animal pretreatment with ciprofibrate results in an eightfold stimulation of ω and ω-1 oxidation, concomitant with a net decrease in the formation of both HETEs and EETs. The isomeric composition of the EETs and of the ω and ω-1 oxidation products formed is also dependent on the type of animal pretreatment. Associated decreases in the amounts of HETEs and the rate of hydrogen peroxide formation suggests a modification of the {"}uncoupler action{"} of arachidonic acid during the function of different cytochromes P-450.",

author = "J. Capdevila and Kim, {Y. R.} and C. Martin-Wixtrom and Falck, {J R} and S. Manna and Estabrook, {R. W.}",

note = "Funding Information: *This paper is dedicated to the memory of Dr. Edward C. Heath. i Supported in part by grants from the USPHS National Institutes of Health (NIGMS 16488, 33541, 31278, BRSG-SO?RR07175-08) and The R. A. Welch Foundation (I-782 and I-959). 2 To whom correspondence",

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AU - Martin-Wixtrom, C.

AU - Falck, J R

AU - Manna, S.

AU - Estabrook, R. W.

N1 - Funding Information: *This paper is dedicated to the memory of Dr. Edward C. Heath. i Supported in part by grants from the USPHS National Institutes of Health (NIGMS 16488, 33541, 31278, BRSG-SO?RR07175-08) and The R. A. Welch Foundation (I-782 and I-959). 2 To whom correspondence

PY - 1985/11/15

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N2 - The regiospecificity of arachidonic acid oxygenation, catalyzed by rat liver microsomal fractions in the presence of NADPH, can be altered by animal pretreatment with a fibric acid type of hypolipidemic drug, ciprofibrate. While microsomal fractions isolated from either control or phenobarbital-treated animals oxygenate arachidonic acid to mainly epoxyeicosatrienoic acids (EETs), animal pretreatment with ciprofibrate results in an eightfold stimulation of ω and ω-1 oxidation, concomitant with a net decrease in the formation of both HETEs and EETs. The isomeric composition of the EETs and of the ω and ω-1 oxidation products formed is also dependent on the type of animal pretreatment. Associated decreases in the amounts of HETEs and the rate of hydrogen peroxide formation suggests a modification of the "uncoupler action" of arachidonic acid during the function of different cytochromes P-450.

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Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450

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